Citations

ABSTRACT Polycystin‐2 (PC2), encoded by the PKD2 gene, mutated in 10‐15% of autosomal‐dominant polycystic kidney disease (ADPKD) patients, is a Ca 2+ ‐permeable cation channel present in kidney epithelia and other tissues. As PC2 was found expressed in B‐lymphoblastoid cells (LCLs) and Ca 2+ signaling pathways are important regulators of B cell function activities, we investigated whether PC2 plays some role in B‐LCLs. In LCLs, PC2 was found mainly in ER membranes but ~8 times less than in kidney HEK293 cells. The same reductions were found in PKD2 and PKD1 RNA; thus, PKD genes maintained, in LCLs, the same reciprocal proportion as they do in kidney cells. In LCLs obtained from subjects carrying PKD2 mutations (PKD2‐LCLs) and showing reduced PC2 levels, intracellular Ca 2+ concentrations evoked by platelet‐activating factor (PAF), were significantly lower than in non‐PKD‐LCLs. This reduction was also found in PKD1‐ LCLs but without PC2 reductions. Likewise, cell proliferation, which is controlled by Ca 2+ , was reduced in PKD2‐ and PKD1‐LCLs. Moreover, in LCLs with PKD2 nonsense mutations, aminoglycoside antibiotics reduced the PC2 defect by promoting readthrough of stop codons. Therefore, PC2 and PC1 are functionally expressed in LCLs, which provide a model, easily obtainable from ADPKD patients, to study PKD gene expression and function.

ABSTRACTBasidiobolomycosis is a chronic subcutaneous infection of the trunk and limbs due toBasidiobolus ranarum.The disease is well known in tropical areas, although recent cases of gastrointestinal basidiobolomycosis have also been reported in Arizona. We describe a young immunocompetent women who had presented with eosinophilia and lung infiltrates. She subsequently died, and diagnosis of disseminated basidiobolomycosis was made on the basis of histological features at autopsy.

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients (between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers (by 1.3–6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling (28–50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA.

Given the high rates of major depressive disorder in primary care settings, routine use of screening measures to assist in identifying depressed individuals is warranted. The Center for Epidemiologic Studies Depression Scale (CES-D) ( Radloff, 1977 ) is a self-rated measure of distress commonly used to screen for depression in primary care settings. The present study was undertaken to confirm the original four-factor model in a sample of low-income women attending primary care clinics (N = 179). Although the original four-factor structure has been replicated in a variety of population groups, internal validity of the measure has not been previously examined in this population sample. A series of confirmatory factor analytic procedures failed to replicate the original four-factor structure or a second-order model. An exploratory analysis, using principal components and a VARIMAX rotation yielded three factors: Depressed Affect/Somatic Symptoms, Positive Affect, and Interpersonal Difficulties. Results of this study add support to previous research documenting an increased somatic presentation of depression in low-income samples. Implications for the use of the CES-D as a screening tool to identify depression in similar primary care samples are discussed.

Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I–restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.

Objective To evaluate the extent to which silicone rubber mandibular implant (Silastic; Dow Corning, Midland, Mich) pressure and placement (supraperiosteal or subperiosteal) affect underlying mandibular resorption. Design A randomized, controlled animal trial. Subjects Ten mixed-breed adult hounds. Interventions Each animal's mandible was implanted with 6 Silastic blocks, 3 inserted supraperiosteally and 3 subperiosteally. Within each grouping of 3 implants, pressure was varied from "minimum" to "moderate" to "maximum" by compressing the implant with titanium miniplates. After 4 months, the animals were killed and their mandibles sectioned for microscopic examination. Results Mandibular resorption occurred in varying degrees beneath all implants by the end of the study period. The extent of resorption was consistent with retrospective studies in humans. No statistically significant difference was found between supraperiosteal or subperiosteal placement of the implants. However, higher-pressure implants tended to produce less resorption than lower-pressure implants. Conclusions While some bone resorption seems inevitable with Silastic mandibular implants, these results would seem to suggest that the placement of implants above or below the periosteum need not be a concern for the surgeon attempting to minimize this consequence. On the other hand, increased pressure may actually decrease resorption, contrary to current assumptions.